N6-methyladenosine (m6A) is a prevalent RNA methylation modification involved in the regulation of degradation, subcellular localization, splicing and local conformation changes of RNA transcripts. High-throughput experiments have demonstrated that only a small fraction of the m6A consensus motifs in mammalian transcriptomes are modified. Therefore, accurate identification of RNA m6A sites becomes emergently important. For the above purpose, here a computational predictor of mammalian m6A site named SRAMP is established. To depict the sequence context around m6A sites, SRAMP combines three random forest classifiers that exploit the positional nucleotide sequence pattern, the K-nearest neighbor information and the position-independent nucleotide pair spectrum features, respectively. SRAMP uses either genomic sequences or cDNA sequences as its input. With either kind of input sequence, SRAMP achieves competitive performance in both cross-validation tests and rigorous independent benchmarking tests. Analyses of the informative features and overrepresented rules extracted from the random forest classifiers demonstrate that nucleotide usage preferences at the distal positions, in addition to those at the proximal positions, contribute to the classification. As a public prediction server, SRAMP is freely available at http://www.cuilab.cn/sramp/.
Comprehensive databases of microRNA–disease associations are continuously demanded in biomedical researches. The recently launched version 3.0 of Human MicroRNA Disease Database (HMDD v3.0) manually collects a significant number of miRNA–disease association entries from literature. Comparing to HMDD v2.0, this new version contains 2-fold more entries. Besides, the associations have been more accurately classified based on literature-derived evidence code, which results in six generalized categories (genetics, epigenetics, target, circulation, tissue and other) covering 20 types of detailed evidence code. Furthermore, we added new functionalities like network visualization on the web interface. To exemplify the utility of the database, we compared the disease spectrum width of miRNAs (DSW) and the miRNA spectrum width of human diseases (MSW) between version 3.0 and 2.0 of HMDD. HMDD is freely accessible at http://www.cuilab.cn/hmdd. With accumulating evidence of miRNA–disease associations, HMDD database will keep on growing in the future.
Prunus mume (mei), which was domesticated in China more than 3,000 years ago as ornamental plant and fruit, is one of the first genomes among Prunus subfamilies of Rosaceae been sequenced. Here, we assemble a 280M genome by combining 101-fold next-generation sequencing and optical mapping data. We further anchor 83.9% of scaffolds to eight chromosomes with genetic map constructed by restriction-site-associated DNA sequencing. Combining P. mume genome with available data, we succeed in reconstructing nine ancestral chromosomes of Rosaceae family, as well as depicting chromosome fusion, fission and duplication history in three major subfamilies. We sequence the transcriptome of various tissues and perform genome-wide analysis to reveal the characteristics of P. mume, including its regulation of early blooming in endodormancy, immune response against bacterial infection and biosynthesis of flower scent. The P. mume genome sequence adds to our understanding of Rosaceae evolution and provides important data for improvement of fruit trees.
The correlation of phenotypic outcomes with genetic variation and environmental factors is a core pursuit in biology and biomedicine. Numerous challenges impede our progress: patient phenotypes may not match known diseases, candidate variants may be in genes that have not been characterized, model organisms may not recapitulate human or veterinary diseases, filling evolutionary gaps is difficult, and many resources must be queried to find potentially significant genotype–phenotype associations. Non-human organisms have proven instrumental in revealing biological mechanisms. Advanced informatics tools can identify phenotypically relevant disease models in research and diagnostic contexts. Large-scale integration of model organism and clinical research data can provide a breadth of knowledge not available from individual sources and can provide contextualization of data back to these sources. The Monarch Initiative (monarchinitiative.org) is a collaborative, open science effort that aims to semantically integrate genotype–phenotype data from many species and sources in order to support precision medicine, disease modeling, and mechanistic exploration. Our integrated knowledge graph, analytic tools, and web services enable diverse users to explore relationships between phenotypes and genotypes across species.
MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression and play vital roles in various biological processes. It has been reported that aberrant regulation of miRNAs was associated with the development and progression of various diseases, but the underlying mechanisms are not fully deciphered. Here, we described our updated TransmiR v2.0 database for more comprehensive information about transcription factor (TF)-miRNA regulations. 3730 TF–miRNA regulations among 19 species from 1349 reports were manually curated by surveying >8000 publications, and more than 1.7 million tissue-specific TF–miRNA regulations were further incorporated based on ChIP-seq data. Besides, we constructed a ‘Predict’ module to query the predicted TF–miRNA regulations in human based on binding motifs of TFs. To facilitate the community, we provided a ‘Network’ module to visualize TF–miRNA regulations for each TF and miRNA, or for a specific disease. An ‘Enrichment analysis’ module was also included to predict TFs that are likely to regulate a miRNA list of interest. In conclusion, with improved data coverage and webserver functionalities, TransmiR v2.0 would be a useful resource for investigating the regulation of miRNAs. TransmiR v2.0 is freely accessible at http://www.cuilab.cn/transmir.
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